Association analysis of an (AC)n repeat polymorphism in the GABA(B) receptor gene and schizophrenia

The human gamma-aminobutyric acid type B (GABA(B)) receptor gene is a candidate gene for schizophrenia due to its chromosomal location and neurobiologic roles. In the present study, association analyses of genetic polymorphisms of the GABA(B) receptor gene with schizophrenia were carried out in 102 unrelated schizophrenic patients and 100 healthy controls, using a polymerase chain reaction-based, single-strand conformational polymorphism analysis. Although the Ala20Val and Gly489Ser mutations were not found in our samples, we found a novel polymorphism of (AC)n dinucleotide repeats located approximately 1.6 kb upstream from the translational start site. No significant difference in allele frequencies was found between controls and patients with schizophrenia (P = 0.0587) using the Monte Carlo method. Significant differences were found between controls and patients with continuous-course schizophrenia (P = 0.0019), and between controls and patients with a positive family history of psychoses (P = 0.0015). These differences, however, were not significant after Bonferroni correction. These data did not support our hypothesis that polymorphisms of the GABA(B) receptor gene may confer vulnerability for schizophrenia.     

Trigeminal neuralgia: evaluation of neuralgic manifestation and site of neurovascular compression with 3D CISS MR imaging and MR angiography

PURPOSE: To evaluate three-dimensional (3D) constructive interference in steady-state (CISS) magnetic resonance (MR) imaging and MR angiography with multiplanar reconstruction (MPR) for detection of neurovascular compression (NVC) in patients with trigeminal neuralgia and to evaluate the relationship between clinical symptoms related to trigeminal branches and those related to the site of trigeminal nerve compression. MATERIALS AND METHODS: Fifty-four consecutive patients with trigeminal neuralgia were examined at 3D CISS imaging and MR angiography with a 1.5-T MR system. Original transverse and four reformatted images were used for image interpretation. Vascular contact with the trigeminal nerve at the root entry zone (REZ) was determined, and the nature of the involved vessels was identified. The position of the blood vessel compressing the nerve was classified into cranial, caudal, medial, or lateral sites. Statistical analysis was performed with the chi2 test or the Fisher exact test between two groups and with the chi2 test among more than two groups. RESULTS: In 12 of 15 patients who underwent surgery, the artery that was considered a responsible vessel at 3D CISS imaging and MR angiography was confirmed as such. In the other three patients, the vein was the responsible vessel, which was detected only at 3D CISS imaging. Sixteen (89%) of 18 patients with symptoms related to the maxillary division had NVC at the medial site of the REZ, while 16 (76%) of 21 patients with symptoms related to the mandibular division had NVC at the lateral site (P <.001, chi2 test). CONCLUSION: 3D CISS MR imaging with MPR is useful in the detection of NVC in patients with trigeminal neuralgia, compared with MR angiography. A close relationship was found between the region of neuralgic manifestation and the site of trigeminal nerve compression.     

CYP3A4*18: it is not rare allele in Japanese population

We sequenced all 13 exons of the CYP3A4 gene derived from 48 Japanese subjects. One subject possess the 20070 T>C mutation in the exon 10 (result in leu293Pro substitution, namely CYP3A4(*)18), as heterozygote. Thus, we investigated the frequency of CYP3A4(*)18 in 118 Japanese population using polymerase chain reaction-restriction fragment length polymorphism with Msp I and determined that the frequency of the CYP3A4(*)18 allele was 1.3%.     

Clinical studies on TUR-P using clinical path: report of 50 cases and review of literature

PURPOSE: This study was undertaken to clarify the usefulness and problems involved in the clinical path of transurethral prostatectomy (TUR-P) in hospital. PATIENTS AND METHODS: The subjects consisted of 50 patients, for whom the Department of Urology, Jikei Medical University Hospital introduced its own clinical path and performed TUR-P during a period of 9 months from July 1999 to March 2000. The mean length of hospital stay, rate of postoperative complications, and the medical insurance claims made by these patients were clarified and compared with those of 73 patients before introduction of the clinical path. RESULTS: With the introduction of the clinical path, the length of hospital stay decreased by an average of 3.4 days and the total medical insurance claims decreased by an average of 18.5%. The rate of postoperative complications before and after introduction was almost equal. CONCLUSION: Our clinical path for TUR-P was well accepted by both patients and comedicals. However, the present medical treatment system in Japan is not as yet prepared to promote the introduction of this clinical path, and it will take some time before this clinical path is introduced on a full scale.     

A case report--a patient with gingiva carcinoma showing complete remission after combination chemotherapy with nedaplatin and 5-fluorouracil

We report a patient showing a complete remission after combination chemotherapy with nedaplatin and 5-fluorouracil (5-FU). A 63-year-old man was admitted to our hospital for advanced carcinoma of gingiva. 5-FU was administered at a dose of 1,000 mg/body (700 mg/m2) by continuous infusion for 120 hours on days 1 to 5. Nedaplatin was administered at a dose of 140 mg/body (90 mg/m2) by drip infusion for 120 minutes on day 5. This combination chemotherapy resulted in a complete remission of the tumor after 2 weeks. There has been no sign of recurrence for 6 months after the chemotherapy.     

Itraconazole-induced cholestasis: involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4

Biliary secretion of bile acids and phospholipids, both of which are essential components of biliary micelles, are mediated by the bile salt export pump (BSEP/ABCB11) and multidrug resistance 3 P-glycoprotein (MDR3/ABCB4), respectively, and their genetic dysfunction leads to the acquisition of severe cholestatic diseases. In the present study, we found two patients with itraconazole (ITZ)-induced cholestatic liver injury with markedly high serum ITZ concentrations. To characterize the effect of ITZ on bile formation in vivo, biliary bile acids and phospholipids were analyzed in ITZ-treated rats, and it was revealed that biliary phospholipids, rather than bile acids, were drastically reduced in the presence of clinically relevant concentrations of ITZ. Moreover, by using MDR3-expressing LLC-PK1 cells, we found that MDR3-mediated efflux of [1?C]phosphatidylcholine was significantly reduced by ITZ. In contrast, BSEP-mediated transport of [3H]taurocholate was not significantly affected by ITZ, which is consistent with our in vivo observations. In conclusion, this study suggests the involvement of the inhibition of MDR3-mediated biliary phospholipids secretion in ITZ-induced cholestasis. Our approach may be useful for analyzing mechanisms of drug-induced cholestasis and evaluating the cholestatic potential of clinically used drugs and drug candidates.     

Cohabitation with farm animals in urban households with and without occupational farm work: associations between participation in educational activities and good hygiene practices in at-risk households cohabiting with farm animals

Objectives  This study was performed to investigate patterns of cohabitation with farm animals in urban households in Vientiane, Lao People’s Democratic Republic, with regard to animal-to-human disease transmission. We also investigated the association between participation in hygiene-related educational activities and good hygiene practices in households with or without cohabitation with animals. Methods  A survey regarding cohabitation with animals, socioeconomic characteristics and participation in educational activities was conducted among 1,497 households randomly sampled from urban districts of Vientiane in 2001. Rates of satisfactory performance of recommended good hygiene practices according to a program commencing in 1996 were compared among households cohabiting with animals with or without participation in educational activities (reference group). Results  Even among households not engaged in agriculture as a major source of income, 54.4, 34.9, 7.9, 3.1 and 35.7% cohabited with chickens, ducks, cattle, buffaloes and dogs, respectively. The percentage of households fulfilling the recommendations for good hygiene practices was 56.7%. The rates of satisfactory hygiene practices among households participating in health education and cohabitating with chickens, ducks or cattle were greater than those in the reference group (OR = 1.7, 95%CI = 1.2, 2.3; OR = 2.0, 95%CI = 1.3, 3.0; OR = 2.3, 95%CI = 1.0, 4.9) regardless of socioeconomic factors. Households cohabiting with animals showed poorer rates of satisfactory hygiene practices than those without animals. Conclusions  Cohabitation with farm animals is common in urban Vientiane regardless of household involvement in agriculture. Further effort is required to improve hygiene conditions, despite some positive effects of health education even in households cohabiting with animals.     

Effectiveness of fosfomycin combined with other antimicrobial agents against multidrug-resistant <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> isolates using the efficacy time index assay

We investigated the effectiveness of fosfomycin combined with other antibiotics, such as piperacillin, cefepime, ceftazidime, imipenem, meropenem, aztreonam, gentamicin, or levofloxacin, against 30 Pseudomonas aeruginosa strains, including multidrug-resistant strains, isolated from clinical specimens, using the efficacy time index (ETI) assay. The assay refers to the result of pharmacokinetics obtained from adult men volunteers, and yields an ETI to evaluate the effect of a combination of antimicrobial agents. With the ETI, based on serum concentration 3 h after the administration of two antimicrobial agents, the effectiveness of antimicrobial combinations was evaluated as follows: poor, ETI < 0.5; fair, 0.5 ≤ ETI < 1; good, 1 ≤ ETI < 8; and excellent, ETI ≥ 8. The combination of fosfomycin and cefepime (efficacy rate [excellent plus good], 76.7%) and fosfomycin/aztreonam (efficacy rate, 76.7%) appeared to be the most effective, followed by fosfomycin/meropenem (efficacy rate, 76.6%), fosfomycin/imipenem (efficacy rate, 73.3%), fosfomycin/ceftazidime (efficacy rate, 70%), fosfomycin/gentamicin (efficacy rate, 70%), fosfomycin/piperacillin (efficacy rate, 66.7%), and fosfomycin/levofloxacin (efficacy rate, 66.7%). Fosfomycin/cefepime, fosfomycin/aztreonam, and fosfomycin/meropenem may be clinically useful in selected patients, particularly for P. aeruginosa. The ETI assay provided information on the minimum inhibitory concentration (MIC) of many pairs of combined antimicrobial agents simultaneously. The ETI assay may be a useful technique with which to investigate the effect of combinations of antimicrobial agents against P. aeruginosa, including multidrug-resistant strains. Received: July 5, 2001 / Accepted: October 29, 2001